A readily exchangeable "free" heme pool appears to play a pivotal role in the synthesis, utilization and degradation of heme in the liver. Since hepatic heme is apparently compartmentalized, such a role would require that the "free" heme pool be intimately associated with these compartments. Several lines of indirect evidence suggest that one such compartment is a phenobarbital-inducible subspecies of hepatic cytochrome P-450 (RT-P450), which by virtue of its extremely rapid turnover characteristics, readily exchanges heme with the "free" heme pool. Since previous findings from our laboratory indicate that exogenous heme, shown to gain access into the "free" heme pool, is readily incorporated into cytochrome P-450, we will investigate whether this incorporation occurs preferentially in RT-P450. In addition, we will also examine, whether turnover of heme of RT-P450 provides heme for the "early labelled bilirubin", appearing in the bile within minutes of an isotopic heme precursor. The heme moiety of RT-P450 is selectively destroyed by various allyl drugs and compounds such as allylisopropylacetamide (AIA). Whether this destruction results in a relative excess of apocytochrome P-450 which can be reconstituted (by supplying heme) to functional RT-P450, will be examined. Such heme-mediated "repair" would have clinical implications in the treatment of patients overdosed with allyl drugs, i.e., allylbarbiturates and diethylallylacetamide. Finally, the potential role of the "free" heme pool in exporting heme from the liver to extrahepatic tissues will also be investigated. This would be of paramount clinical relevance in heme-deficient states such as the hepatic porphyrias, in which the export of hepatic heme to these tissues could be critically impaired.